[Pharmacology of estrogens and progestogens and cardiovascular risk]

The rationale for oestrogen replacement therapy relies mainly on two types of evidence, both of which are flawed: (1) the relative protection of women in premenopausal status against cardiovascular diseases and the increase of risk following menopause; (2) data from observational studies that showed a lower prevalence of cardiovascular events in women taking hormone replacement therapy (HRT) compared with those not taking such treatment (OR = 0.65; 95 per cent CI: 0.59-0.71). Behind the former evidence there is the assumption that the difference in risk before and after menopause is mostly due to the lack of ovarian oestrogens in post-menopausal women. This is indeed a strong assumption since there are many other changes during and after menopause. The second type of evidence assumes that the ORs given by the observational studies are unbiased. In fact, there are reliable data suggesting that women taking and not taking HRT are different in many respects, especially in their concerns for their health. This dimension has been proposed as an explanation for the correlation between compliance with placebo and survival. The only reliable approach is to perform adequately sized and long-term follow-up randomized trials. Although they should not be viewed as conclusive, the results of the first completed trial do not support the hypothesis that HRT is beneficial in women with a history of coronary disease.